The tenet of this proposal is that FF-ICR mass spectrometers are sufficiently advanced and the required methodologies are sufficiently well proven to place such an instrument in a core facility like the Keck Laboratory for the purpose of bringing quantitative protein expression and phosphorylation analysis within reach of 346 Yale and 633 non-Yale principal investigators from 224 institutions who used this Laboratory in 2000. With several genome projects completed or nearing completion, interest is rapidly being directed towards proteomics--including protein expression and understanding protein function and its control by post-translational modifications. A major goal of the Keck Laboratory is to begin to bridge the large gap between what is theoretically possible with FT-ICR mass spectrometry and what is actually available to most NIH-supported investigators. Rather than only reading about break through protein expression methodologies like isotope coded affinity tags, we would like many more NIH-supported investigators to be able to bring these technologies to bear on the challenging biomedical problems they seek to solve. The strengths of this proposal include the diverse and productive user base that supports the Keck Laboratory; the demonstrated ability of this Lab to bring mass spectrometric and other technologies to bear on hundreds of difficult research problems that confront these users; the technical and organizational expertise to bring the requested instrumentation "on-line" and to design, optimize, and implement well defined services; the long term stability of the Keck Lab and its proven ability to continually operate and maintain sophisticated biotechnological instrumentation; the rapid progress of the Keck Microarray Resource - which provides an excellent opportunity to compare mRNA versus protein expression analysis; and the extensive support and "infrastructure" which is in place to ensure the success of the proposed research. This support ranges from the MS and separation technology expertise needed to ensure maximum benefit is derived from the requested instrumentation to the bioinformatic, computer programming, and biostatistical expertise needed to ensure the resulting data is properly interpreted and is archived such that it can be readily retrieved, subjected to further analysis, and cross-correlated with other relevant data. We believe the requested instrument would make a major contribution to biomedical research that would extend far beyond Yale University.